Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Abdellatif, M; Trummer-Herbst, V; Koser, F; Durand, S; Adão, R; Vasques-Nóvoa, F; Freundt, JK; Voglhuber, J; Pricolo, MR; Kasa, M; Türk, C; Aprahamian, F; Herrero-Galán, E; Hofer, SJ; Pendl, T; Rech, L; Kargl, J; Anto-Michel, N; Ljubojevic-Holzer, S; Schipke, J; Brandenberger, C; Auer, M; Schreiber, R; Koyani, CN; Heinemann, A; Zirlik, A; Schmidt, A; von Lewinski, D; Scherr, D; Rainer, PP; von Maltzahn, J; Mühlfeld, C; Krüger, M; Frank, S; Madeo, F; Eisenberg, T; Prokesch, A; Leite-Moreira, AF; Lourenço, AP; Alegre-Cebollada, J; Kiechl, S; Linke, WA; Kroemer, G; Sedej, S.
Nicotinamide for the treatment of heart failure with preserved ejection fraction.
Sci Transl Med. 2021; 13(580): eabd7064
Doi: 10.1126/scitranslmed.abd7064
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- Führende Autor*innen der Med Uni Graz
- Abdellatif Mahmoud
- Sedej Simon
- Co-Autor*innen der Med Uni Graz
- Anto Michel Nathaly
- Auer Martina
- Eisenberg Tobias
- Frank Sasa
- Heinemann Akos
- Holzer Senka
- Kargl Julia
- Kasa Michael
- Koyani Chintan Navinchandra
- Prokesch Andreas
- Rainer Peter
- Rech Cara Lavinia Shirin
- Scherr Daniel
- Schmidt Albrecht
- Schreiber Renate
- Trummer-Herbst Viktoria
- Voglhuber Julia
- von Lewinski Dirk
- Zirlik Andreas
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- Abstract:
- Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent and intractable form of cardiac decompensation commonly associated with diastolic dysfunction. Here, we show that diastolic dysfunction in patients with HFpEF is associated with a cardiac deficit in nicotinamide adenine dinucleotide (NAD+). Elevating NAD+ by oral supplementation of its precursor, nicotinamide, improved diastolic dysfunction induced by aging (in 2-year-old C57BL/6J mice), hypertension (in Dahl salt-sensitive rats), or cardiometabolic syndrome (in ZSF1 obese rats). This effect was mediated partly through alleviated systemic comorbidities and enhanced myocardial bioenergetics. Simultaneously, nicotinamide directly improved cardiomyocyte passive stiffness and calcium-dependent active relaxation through increased deacetylation of titin and the sarcoplasmic reticulum calcium adenosine triphosphatase 2a, respectively. In a long-term human cohort study, high dietary intake of naturally occurring NAD+ precursors was associated with lower blood pressure and reduced risk of cardiac mortality. Collectively, these results suggest NAD+ precursors, and especially nicotinamide, as potential therapeutic agents to treat diastolic dysfunction and HFpEF in humans. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.